The Role of TOMM40 in Cardiovascular Mortality and Conduction Disorders: An Observational Study.

Aims: TOMM40 single nucleotide polymorphism (SNP) rs2075650 consists of allelic variation c.275-31A > G and it has been linked to Alzheimer disease, apolipoprotein and cholesterol levels and other risk factors. However, data on its role in cardiovascular disorders are lacking. The first aim of the study is to evaluate mortality according to TOMM40 genotype in a cohort of selected patients affected by advanced atherosclerosis. Second aim was to investigate the relationship between Xg and AA alleles and the presence of conduction disorders and implantation of defibrillator (ICD) or pacemaker (PM) in our cohort. Materials and Methods: We enrolled 276 patients (mean age 70.16 ± 7.96 years) affected by hemodynamic significant carotid stenosis and/or ischemia of the lower limbs of II or III stadium Fontaine. We divided the population into two groups according to the genotype (Xg and AA carriers). We evaluated several electrocardiographic and echocardiographic parameters, including heart rate, rhythm, presence of right and left bundle branch block (LBBB and RBBB), PR interval, QRS duration and morphology, QTc interval, and left ventricular ejection fraction (LVEF). We clinically followed these patients for 82.53 ± 30.02 months and we evaluated the incidence of cardiovascular events, number of deaths and PM/ICD implantations. Results: We did not find a difference in total mortality between Xg and AA carriers (16.3 % vs. 19.4%; p = 0.62). However, we found a higher mortality for fatal cardiovascular events in Xg carriers (8.2% vs. 4.4%; HR = 4.53, 95% CI 1.179-17.367; p = 0.04) with respect to AA carriers. We noted a higher percentage of LBBB in Xg carriers (10.2% vs. 3.1%, p = 0.027), which was statistically significant. Presence of right bundle branch block (RBBB) was also higher in Xg (10.2% vs. 4.4%, p = 0.10), but without reaching statistically significant difference compared to AA patients. We did not observe significant differences in heart rate, presence of sinus rhythm, number of device implantations, PR and QTc intervals, QRS duration and LVEF between the two groups. At the time of enrolment, we observed a tendency for device implant in Xg carriers at a younger age compared to AA carriers (58.50 ± 0.71 y vs. 72.14 ± 11.11 y, p = 0.10). During the follow-up, we noted no statistical difference for new device implantations in Xg respect to AA carriers (8.2% vs. 3.5%; HR = 2.384, 95% CI 0.718-7.922; p = 0.156). The tendency to implant Xg at a younger age compared to AA patients was confirmed during follow-up, but without reaching a significant difference(69.50 ± 2.89 y vs. 75.63 ± 8.35 y, p = 0.074). Finally, we pointed out that Xg carriers underwent device implantation 7.27 ± 4.43 years before AA (65.83 ± 6.11 years vs. 73.10 ± 10.39 years) and that difference reached a statistically significant difference (p = 0.049) when we considered all patients, from enrollment to follow-up. Conclusions: In our study we observed that TOMM40 Xg patients affected by advanced atherosclerosis have a higher incidence of developing fatal cardiovascular events, higher incidence of LBBB and an earlier age of PM or ICD implantations, as compared to AA carriers. Further studies will be needed to evaluate the genomic contribution of TOMM40 SNPs to cardiovascular deaths and cardiac conduction diseases.

Electrocardiogram in Friedreich's ataxia: A short-term surrogate endpoint for treatment efficacy.

Friedreich's ataxia is a rare degenerative neuromuscular disorder, caused by a homozygous GAA triplet repeat expansion in the frataxin (FXN) gene, with a broad clinical phenotype characterized by progressive gait and limb ataxia, dysarthria, and loss of lower limb reflexes; cardiac involvement is represented by hypertrophic cardiomyopathy, ventricular arrhythmias, and sudden cardiac deaths. Currently, no definite therapy is available, while many drugs are under investigation; for this reasons, we need markers of short- and long-term treatment efficacy acting on different tissue for trial evaluation. We describe the case of a 21-year-old patient affected by Friedreich's ataxia on wheel-chair, with initial cardiac involvement and electrocardiographic features characterized by thiamine treatment-related negative T wave and QTc variations. We discuss plausible physiopathology and potential ECG role implications as an intermediate marker of treatment response in future clinical trials considering patients affected by Friedreich's ataxia.

Double missense mutations in cardiac myosin-binding protein C and myopalladin genes: A case report with diffuse coronary disease, complete atrioventricular block, and progression to dilated cardiomyopathy.

Cardiomyopathies caused by double gene mutations are rare but conferred a remarkably increased risk of end-stage progression, arrhythmias, and poor outcome. Compound genetic mutations leading to complex phenotype in the setting of cardiomyopathies represent an important challenge in clinical practice, and genetic tests allow risk stratification and personalized clinical management of patients. We report a case of a 50-year-old woman with congestive heart failure characterized by dilated cardiomyopathy, diffuse coronary disease, complete atrioventricular block, and missense mutations in cardiac myosin-binding protein C (MYBPC3) and myopalladin (MYPN). We discuss the plausible role of genetic profile in phenotype determination.

Role of Subclinical Iatrogenic Hyperthyroidism in the Setting of Heart Disease and Arrhythmic Burden.

BACKGROUND: Subclinical hyperthyroidism is defined by a subnormal serum thyroidstimulating hormone (TSH) level with normal free thyroxine (FT4) and free triiodothyronine (FT3) levels. Its prevalence varies from 0.6% to 16% in the elderly and can increase to 20% in patients receiving thyroid hormone replacement therapy. Thyroid disease and/or replacement therapy are frequently associated with cardiovascular involvement. CASES PRESENTATION: We report three clinical cases of patients with initial subclinical hyperthyroidism and cardiological manifestations, including supraventricular and ventricular extrasystoles, prolapse of the mitral valve with severe regurgitation, higher mean heart rate and deterioration of the arrhythmias on arrhythmogenic dysplasia substrate. CONCLUSION: We discuss the role of appropriate and early correction of thyroid dysfunction in improving cardiological manifestations.

Inappropriate shock and percutaneous cardiac intervention: A lesson to learn in the cath lab.

Coronary disease is a common condition in patients affected by heart failure with severely reduced ejection fraction (HFrEF). This condition represents an indication for implantable cardioverter defibrillator (ICD) in order to reduce the risk of sudden death related to arrhythmias. Nevertheless, inappropriate shocks are associated with worse quality of life, hospitalization, and death. We present the case of an inappropriate shock related to percutaneous coronary intervention during the insertion and advancement of the guidewire into the left anterior descending artery (LAD) in a patient with an ICD. Physicians' awareness about the clinical implication of noise arising during a coronary procedure is very important in patients with an ICD or pacemaker, to avoid inappropriate shock or pacing inhibition and to raise the possibility of lead implantation in or helix protrusion into the coronary lumen.

Rate and Predictors of Permanent Pacemaker Implantation After Transcatheter Aortic Valve Implantation: Current Status.

Transcather aortic valve implantation (TAVI) has become a safe and indispensable treatment option for patients with severe symptomatic aortic stenosis who are at high surgical risk. Recently, outcomes after TAVI have improved significantly and TAVI has emerged as a qualified alternative to surgical aortic valve replacement in the treatment of intermediate risk patients and greater adoption of this procedure is to be expected in a wider patients population, including younger patients and low surgical risk patients. However since the aortic valve has close spatial proximity to the conduction system, conduction anomalies are frequently observed in TAVI. In this article, we aim to review the key aspects of pathophysiology, current incidence, predictors and clinical association of conduction anomalies following TAVI.

Cardiac arrest caused by Barlow's syndrome or by stress cardiomyopathy?

We describe a case of out-of-hospital Cardiac Arrest (CA) in a patient with Barlow's Syndrome (BS) and features of Stress Cardiomyopathy (SC) (or Apical Ballooning Syndrome or Tako-Tsubo). The patient experienced CA during physical stress and was resuscitated thanks to DC-Shock. The Electrocardiogram (ECG) after resuscitation was unremarkable. In the reported case the documented severe hypokalemia, with the physical stress, could have triggered the CA, probably of tachyarrhythmic origin. However, in the reported case, the echocardiographic, coronarographic and ventriculographic features, were surprisingly indistinguishable from those of the SC. In conclusion it is impossible to say if, in our patient, the CA has been caused by BS or by SC. However, even if CA has been probably caused by the BS, we hypothesize that the CA, in its turn determined, might have caused the SC via stress mechanisms. In few words, the CA is a complication of SC, but should probably be regarded also as a cause of SC.

Atrial fibrillation ablation strategies for paroxysmal patients: randomized comparison between different techniques.

BACKGROUND: Whether different ablation strategies affect paroxysmal atrial fibrillation (AF) long-term freedom from AF/atrial tachyarrhythmia is unclear. We sought to compare the effect of 3 different ablation approaches on the long-term success in patients with paroxysmal AF. METHODS AND RESULTS: One hundred three consecutive patients with paroxysmal AF scheduled for ablation and presenting in the electrophysiology laboratory in AF were selected for this study. Patients were randomized to pulmonary vein antrum isolation (PVAI; n=35) versus biatrial ablation of the complex fractionated atrial electrograms (CFAEs; n=34) versus PVAI followed by CFAEs (n=34). Patients were given event recorders and followed up at 3, 6, 9, 12, and 15 months postablation. There was no statistical significant difference between the groups in term of sex, age, AF duration, left atrial size, and ejection fraction. At 1 year follow-up, freedom from AF/atrial tachyarrhythmia was documented in 89% of patients in the PVAI group, 91% in the PVAI plus CFAEs group, and 23% in the CFAEs group (P<0.001) after a single procedure and with antiarrhythmic drugs. CONCLUSIONS: No difference in terms of success rate was seen between PVAI alone and PVAI associated with defragmentation. CFAEs ablation alone had the smallest impact on AF recurrences at 1-year follow-up. These results suggest that antral isolation is sufficient to treat most patients with paroxysmal AF.

Ablation for longstanding permanent atrial fibrillation: results from a randomized study comparing three different strategies.

BACKGROUND: This prospective multicenter randomized study aimed to compare the efficacy of 3 common ablation methods used for longstanding permanent atrial fibrillation (AF). METHODS: A total of 144 patients with longstanding permanent AF (median duration 28 months) were randomly assigned to circumferential pulmonary vein ablation (CPVA, group 1, n = 47), to pulmonary vein antrum isolation (PVAI, group 2, n = 48) or to a hybrid strategy combining ablation of complex fractionated or rapid atrial electrograms (CFAE) in both atria followed by a pulmonary vein antrum isolation (CFAE + PVAI, group 3, n = 49). RESULTS: Scarring in the left atrium and structural heart disease/hypertension were present in most patients (65%). After a mean follow-up of 16 months, 11% of patients in group 1, 40% of patients in group 2 and 61% of patients in group 3 were in sinus rhythm after one procedure and with no antiarrhythmic drugs (P < .001). Sinus rhythm maintenance would increase respectively to 28% (group 1), 83% (group 2), and 94% (group 3) after 2 procedures and with antiarrhythmic drugs (AADs, P < .001). The AF terminated during ablation, either by conversion to sinus rhythm or organization into an atrial tachyarrhythmia, in 13% of patients (group 1), 44% (group 2), and 74% (group 3) respectively. CFAE alone, performed as the first step of the ablation in group 3, organized AF in only 1 patient. CONCLUSION: In this study, the hybrid AF ablation strategy including antrum isolation and CFAE ablation had the highest likelihood of maintaining sinus rhythm in patients with longstanding permanent AF. Electrical isolation of the PVs, although inadequate if performed alone, is relevant to achieve long-term sinus rhythm maintenance after ablation. Bi-atrial CFAE ablation had a minimal impact on AF termination during ablation.

Pulmonary-vein isolation for atrial fibrillation in patients with heart failure.

BACKGROUND: Pulmonary-vein isolation is increasingly being used to treat atrial fibrillation in patients with heart failure. METHODS: In this prospective, multicenter clinical trial, we randomly assigned patients with symptomatic, drug-resistant atrial fibrillation, an ejection fraction of 40% or less, and New York Heart Association class II or III heart failure to undergo either pulmonary-vein isolation or atrioventricular-node ablation with biventricular pacing. All patients completed the Minnesota Living with Heart Failure questionnaire (scores range from 0 to 105, with a higher score indicating a worse quality of life) and underwent echocardiography and a 6-minute walk test (the composite primary end point). Over a 6-month period, patients were monitored for both symptomatic and asymptomatic episodes of atrial fibrillation. RESULTS: In all, 41 patients underwent pulmonary-vein isolation, and 40 underwent atrioventricular-node ablation with biventricular pacing; none were lost to follow-up at 6 months. The composite primary end point favored the group that underwent pulmonary-vein isolation, with an improved questionnaire score at 6 months (60, vs. 82 in the group that underwent atrioventricular-node ablation with biventricular pacing; P<0.001), a longer 6-minute-walk distance (340 m vs. 297 m, P<0.001), and a higher ejection fraction (35% vs. 28%, P<0.001). In the group that underwent pulmonary-vein isolation, 88% of patients receiving antiarrhythmic drugs and 71% of those not receiving such drugs were free of atrial fibrillation at 6 months. In the group that underwent pulmonary-vein isolation, pulmonary-vein stenosis developed in two patients, pericardial effusion in one, and pulmonary edema in another; in the group that underwent atrioventricular-node ablation with biventricular pacing, lead dislodgment was found in one patient and pneumothorax in another. CONCLUSIONS: Pulmonary-vein isolation was superior to atrioventricular-node ablation with biventricular pacing in patients with heart failure who had drug-refractory atrial fibrillation. (ClinicalTrials.gov number, NCT00599976.)

Anomalous origin of the left coronary artery from the pulmonary artery in an elderly patient, football player in youth.

Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital defect. Without surgical treatment, approximately 90% of infants die within the first year of life. Late presentation in the adult or elderly is rare. Factors that may lead to survival in advanced age include the development of intercoronary collaterals. Furthermore, the risk of sudden cardiac death due to ischaemic malignant ventricular dysrhythmias exists even in asymptomatic adult patients and, classically, is precipitated by exercise. We report the case of a 67-year-old man, a football player in his youth, always asymptomatic until presentation at our centre for symptomatic sustained ventricular tachycardia and shortness of breath on exertion. We show the features of the ECG, transthoracic echocardiography, angiography study of the coronary and the pulmonary system, myocardial basal and stress gated single photon emission computed tomography with Tc-tetrofosmin and cardiac CT 64 slices. The patient was referred to cardiac surgery. We believe that this patient's favourable course may be ascribed to the large network of collaterals from the right coronary artery supplying the entire heart. However, the exact reason why these favourable evolutions (both vascular and clinical) occur only in some individuals remains largely unknown.

Double rhythm in double heart.

We describe the case of a patient with heterotopic transplantation, sinus rhythm originating from the donor heart, ventricular fibrillation of the native heart and right severe decompensation. The double rhythm was easily detected with a surface ECG and the transthoracic echocardiogram, both performed in the left conventional and in the right modified mode. The patient was successfully treated with direct current shock with quick restoration of native heart synchronization and clinical relief of symptoms.

Pulmonary vein antral isolation using an open irrigation ablation catheter for the treatment of atrial fibrillation: a randomized pilot study.

OBJECTIVES: We sought to test how catheter ablation using an open irrigation catheter (OIC) compares with standard catheters for pulmonary vein antrum isolation. BACKGROUND: Open irrigation catheters have the advantage of delivering greater power without increasing the temperature of the catheter tip, which enables deeper and wider lesions without the formation of coagulum on catheters. METHODS: Catheter ablation was performed using an 8-mm catheter (8MC) or an OIC. Patients were randomized to 3 groups: 8MC; OIC-1, OIC with a higher peak power (50 W); and OIC-2, OIC with lower peak power (35 W). RESULTS: A total of 180 patients were randomized to the 3 treatment strategies. Isolation of pulmonary vein antra was achieved in all patients. The freedom from atrial fibrillation was significantly greater in the 8MC and OIC-1 groups compared with the OIC-2 group (78%, 82%, and 68%, respectively, p = 0.043). Fluoroscopy time was lower in OIC-1 compared with OIC-2 and 8MC (28 +/- 1 min, 53 +/- 2 min, and 46 +/- 2 min, respectively, p = 0.001). The mean left atrium instrumentation time was lower in the OIC-1 compared with the OIC-2 and 8MC groups (59 +/- 3 min, 90 +/- 5 min, and 88 +/- 4 min, respectively, p = 0.001). However, there was a greater incidence of "pops" in the OIC-1 (100%, 0%, 0%, p < 0.001) along with higher incidences of pericardial effusion (20%, 0%, 0%, p < 0.001) and gastrointestinal complaints (17% in OIC-1, 3% in 8MC, and 5% in OIC-2, p = 0.031). CONCLUSIONS: Although there was a decrease in fluoroscopy and left atrium instrumentation time with the use of OIC at higher power, this setting was associated with increased cardiovascular and gastrointestinal complications.

Right and left ventricular activation sequence in patients with heart failure and right bundle branch block: a detailed analysis using three-dimensional non-fluoroscopic electroanatomic mapping system.

UNLABELLED: Three-dimensional mapping in RBBB and heart failure. INTRODUCTION: Recently, right bundle branch block (RBBB) was proved to be an important predictor of mortality in heart failure (HF) patients as much as left bundle branch block (LBBB). We characterized endocardial right ventricular (RV) and left ventricular (LV) activation sequence in HF patients with RBBB using a three-dimensional non-fluoroscopic electroanatomic contact mapping system (3D-Map) in order to provide the electrophysiological background to understand whether these patients can benefit from cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Using 3D-Map, RV and LV activation sequences were studied in 100 consecutive HF patients. Six of these patients presented with RBBB QRS morphology. The maps of these patients were analyzed and compared post hoc with those of the other 94 HF patients presenting with LBBB. Clinical and hemodynamic profile was significantly worse in RBBB group compared to LBBB. Patients with RBBB showed significantly longer time to RV breakthrough (P<0.001), longer activation times of RV anterior and lateral regions (P<0.001), and longer total RV endocardial activation time (P<0.02) compared to patients with LBBB. Time to LV breakthrough was significantly shorter in patients with RBBB (P<0.001), while total and regional LV endocardial activation times were not significantly different between the two groups. CONCLUSIONS: Degree of LV activation delay is similar between HF patients with LBBB and RBBB. Moreover, patients with RBBB have larger right-sided conduction delay compared to patients with LBBB. The assessment of these electrical abnormalities is important to understand the rationale for delivering CRT in HF patients with RBBB.